The median nerve is susceptible to compression in the wrist, leading to carpal tunnel syndrome (CTS). CTS is the most common compression neuropathy and have an immense impact on national health care, worker productivity, and quality of life. Despite its high prevalence and public health cost, our understanding of CTS is limited, and the management of CTS awaits improvement. The central notion of this project is that hand sensorimotor function is sensitive to peripheral median neuropathy and that the central nervous system is affected by CTS, causing the associated sensorimotor deficit. We will investigate this notion with quantifiable sensorimotor data from novel biomechanical and neurophysiological studies. This project has three aims consisting of biomechanical, neurophysiological and translational research. The first aim is to investigate CTS-induced pathokinematic and pathokinetic performance using dexterous manual tasks of thumb opposition, reach-to-pinch, precision grip, and finger pressing. The second aim is to investigate the neurophysiological implications of chronic peripheral neuropathy (i.e., CTS) on the central nervous system by evaluating corticomuscular coupling and stretch reflex. The third aim is to identify novel biomechanical and neurophysiological markers for CTS cases using machine learning and classification algorithms. The results of this project will elucidate the pathological mechanisms and behavioral manifestations of CTS and aid in the development of new strategies for diagnosis, evaluation, rehabilitation, and treatment of this disorder. More generally, CTS as a chronic neuropathy serves as an effective model to study sensorimotor mechanisms of the peripheral and central nervous systems. In addition, the methodology developed in this project is applicable to other neuromuscular disorders.